The long range objective of this research proposal is to more closely define in normal and diabetic man the effect of glucose on the disposition of amino acids by the body after oral protein ingestion. This study is feasible because of our ability to isolate the liver in the dog and the splanchnic bed in man by 1) surgically implanting catheters two weeks prior to study in the hepatic and portal veins and femoral artery of the dog and 2) by catheterizing the hepatic vein and brachial artery in normal man on the day of study. Multiplication of the arterio-venous difference thus obtained by the hepatic blood flow measured using indocyanine green allows calculation of net balance of amino acids and glucose across both the entire splanchnic bed and the liver and gut in the dog. Using these techniques, we want to accomplish the following in dog and ultimately in man: 1) to determine the effect of glucose (oral and intravenous) on the absorption (arterio-portal venous difference X flow) and hepatic uptake of total and individual amino acids after beef ingestion; 2) to determine whether the delayed rise in circulating amino acids after protein and glucose ingestion is mediated via decreased pancreatic exocrine secretion; 3) to quantify the role of plasma glucagon in determining the rate of hepatic amino acid extraction after protein loading; and 4) to examine the influence of glucose on amino acid disposition after protein ingestion in diabetes. Preliminary data suggest that the ingestion of glucose with beef results in a delay in amino acid absorption until the glucose load is dispersed whereupon amino acid absorption increases. Diabetic man may be insensitive to this retarding effect of glucose on amino acid absorption leading to hyperaminoacidemia, increased glucagon secretion, and deterioration of glucose tolerance. Thus, the proposed studies are designed to provide considerable insight into the regulation of amino acid disposition after protein ingestion in normal and diabetic man.